Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~

Cancer Cell Metabolism Gene Database

Cancer Cell Metabolism Gene DB

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	Gene Summary
	Phenotypic Information (metabolism pathway, cancer, disease, phenome)
	Mutations : SVs, CNVs, SNVs
	Gene expression: GE, Protein, DEGE, CNV vs GE
	Gene-Gene Network Information: Co-Expression Network, Interacting Genes & KEGG
	Pharmacological Information: Drug-Gene Network
	Cross referenced IDs

Gene Summary for EIF4E

Basic gene info.	Gene symbol	EIF4E
	Gene name	eukaryotic translation initiation factor 4E
	Synonyms	AUTS19\|CBP\|EIF4E1\|EIF4EL1\|EIF4F
	Cytomap	UCSC genome browser: 4q23
	Genomic location	chr4 :99799606-99850243
	Type of gene	protein-coding
	RefGenes	NM_001130678.1, NM_001130679.1,NM_001968.3,
	Ensembl id	ENSG00000151247
	Description	eIF-4EeIF-4F 25 kDa subuniteukaryotic translation initiation factor 4E-like 1mRNA cap-binding protein
	Modification date	20141207
dbXrefs	MIM : 133440
	HGNC : HGNC
	HPRD : 00591
Protein	UniProt: P06730 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_EIF4E
	BioGPS: 1977
	Gene Expression Atlas: ENSG00000151247
	The Human Protein Atlas: ENSG00000151247
Pathway	NCI Pathway Interaction Database: EIF4E
	KEGG: EIF4E
	REACTOME: EIF4E
	ConsensusPathDB
	Pathway Commons: EIF4E
Metabolism	MetaCyc: EIF4E
	HUMANCyc: EIF4E
Regulation	Ensembl's Regulation: ENSG00000151247
	miRBase: chr4 :99,799,606-99,850,243
	TargetScan: NM_001130678
	cisRED: ENSG00000151247
Context	iHOP: EIF4E
	cancer metabolism search in PubMed: EIF4E
	UCL Cancer Institute: EIF4E
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of EIF4E in cancer cell metabolism	1. Chatterjee A, Mukhopadhyay S, Tung K, Patel D, Foster DA (2015) Rapamycin-induced G1 cell cycle arrest employs both TGF-beta and Rb pathways. Cancer Lett 360: 134-140. doi: 10.1016/j.canlet.2015.01.043. pmid: 4415112. go to article 2. Su X, Yu Y, Zhong Y, Giannopoulou EG, Hu X, et al. (2015) Interferon-gamma regulates cellular metabolism and mRNA translation to potentiate macrophage activation. Nat Immunol. doi: 10.1038/ni.3205. go to article 3. Li SH, Chen CH, Lu HI, Huang WT, Tien WY, et al. (2015) Phosphorylated p70S6K expression is an independent prognosticator for patients with esophageal squamous cell carcinoma. Surgery 157: 570-580. doi: 10.1016/j.surg.2014.10.014. go to article

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Phenotypic Information for EIF4E(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: EIF4E
	Familial Cancer Database: EIF4E

* This gene is included in those cancer gene databases.

						.
Oncogene ¹	Tumor Suppressor gene ²	Cancer Gene Census ³	CancerGenes ⁴	Network of Cancer Gene ⁵	Significant driver gene in	Therapeutic Vulnerabilities in Cancer¹

cf) number; DB name
1 Oncogene; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
2 Tumor Suppressor gene; https://bioinfo.uth.edu/TSGene/,
3 Cancer Gene Census; http://www.nature.com/nrc/journal/v4/n3/abs/nrc1299.html,
4 CancerGenes; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
5 Network of Cancer Gene; http://ncg.kcl.ac.uk/index.php,
1Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
REACTOME_METABOLISM_OF_PROTEINS REACTOME_METABOLISM_OF_MRNA REACTOME_METABOLISM_OF_RNA

Others
OMIM	133440; gene. 615091; phenotype.
Orphanet	106; Autism.
Disease	KEGG Disease: EIF4E
	MedGen: EIF4E (Human Medical Genetics with Condition)
	ClinVar: EIF4E
Phenotype	MGI: EIF4E (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: EIF4E

Mutations for EIF4E

* Under tables are showing count per each tissue to give us broad intuition about tissue specific mutation patterns.You can go to the detailed page for each mutation database's web site.

Structural Variants in COSMIC : go to COSMIC mutation histogram

- Statistics for Tissue and Mutation type

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- For Inter-chromosomal Variations

There's no inter-chromosomal structural variation.

- For Intra-chromosomal Variations

* Intra-chromosomal variantions includes 'intrachromosomal amplicon to amplicon', 'intrachromosomal amplicon to non-amplified dna', 'intrachromosomal deletion', 'intrachromosomal fold-back inversion', 'intrachromosomal inversion', 'intrachromosomal tandem duplication', 'Intrachromosomal unknown type', 'intrachromosomal with inverted orientation', 'intrachromosomal with non-inverted orientation'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	EIF4E	chr4	99837092	99837112	TSPAN5	chr4	99483013	99483033

cf) Tissue number; Tissue name (1;Breast, 2;Central_nervous_system, 3;Haematopoietic_and_lymphoid_tissue, 4;Large_intestine, 5;Liver, 6;Lung, 7;Ovary, 8;Pancreas, 9;Prostate, 10;Skin, 11;Soft_tissue, 12;Upper_aerodigestive_tract)

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows EIF4E related fusion information.

ID	Head Gene						Tail Gene
Accession	Gene_a	qStart_a	qEnd_a	Chromosome_a	tStart_a	tEnd_a	Gene_a	qStart_a	qEnd_a	Chromosome_a	tStart_a	tEnd_a
BF879888	ABCA1	7	294	9	107587996	107589344	EIF4E	288	486	4	99809803	99810001
DA724990	EIF4E	1	148	4	99823025	99850284	UBXN7	144	543	3	196118683	196134267

Other DBs for Structural Variants

Structural Variants in Ensembl: go to Ensembl Structural variation

Structural Variants in dbVar: go to dbVar

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Copy Number Variations in COSMIC : go to COSMIC mutation CNV/Expr

There's no copy number variation information in COSMIC data for this gene.

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SNV Counts per Each Loci in COSMIC data : go to COSMIC point mutation

: Non-synonymous mutation, : Synonymous mutation, Circle size denotes number of samples.
Maximum mutation count=2

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=9)	Stat. for Synonymous SNVs (# total SNVs=5)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=0)
There's no deleted snv.	There's no inserted snv.

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Top 10 SNVs Having the Most Samples in COSMIC data

* When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site,primary_histology,mutation(aa),pubmedID.

GRCh37 position	Mutation(aa)	Unique sampleID count
chr4:99823101-99823101	p.T17T	2
chr4:99823081-99823081	p.S24C	1
chr4:99808247-99808247	p.R128C	1
chr4:99823086-99823086	p.T22T	1
chr4:99802209-99802209	p.G208G	1
chr4:99808250-99808250	p.D127N	1
chr4:99823099-99823099	p.E18V	1
chr4:99802261-99802261	p.P191L	1
chr4:99808251-99808251	p.L126L	1
chr4:99802262-99802262	p.P191A	1

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SNV Counts per Each Loci in TCGA data

: non-synonymous mutation, : synonymous mutation, Circle size denotes number of samples.
maximum mutation count=2

Point Mutation/ Tissue ID	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
# sample	1			1					1			3	1			1	2	3		4
# mutation	1			1					1			4	1			1	2	3		4
nonsynonymous SNV	1								1			3					1	1		2
synonymous SNV				1								1	1			1	1	2		2

cf) Tissue ID; Tissue type (1; BLCA[Bladder Urothelial Carcinoma], 2; BRCA[Breast invasive carcinoma], 3; CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], 4; COAD[Colon adenocarcinoma], 5; GBM[Glioblastoma multiforme], 6; Glioma Low Grade, 7; HNSC[Head and Neck squamous cell carcinoma], 8; KICH[Kidney Chromophobe], 9; KIRC[Kidney renal clear cell carcinoma], 10; KIRP[Kidney renal papillary cell carcinoma], 11; LAML[Acute Myeloid Leukemia], 12; LUAD[Lung adenocarcinoma], 13; LUSC[Lung squamous cell carcinoma], 14; OV[Ovarian serous cystadenocarcinoma ], 15; PAAD[Pancreatic adenocarcinoma], 16; PRAD[Prostate adenocarcinoma], 17; SKCM[Skin Cutaneous Melanoma], 18:STAD[Stomach adenocarcinoma], 19:THCA[Thyroid carcinoma], 20:UCEC[Uterine Corpus Endometrial Carcinoma])

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Top 10 SNVs Having the Most Samples in TCGA data

* We represented just top 10 SNVs. When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site, primary_histology, mutation(aa), pubmedID.

Genomic Position	Mutation(aa)	Unique sampleID count
chr4:99823086	p.T42T,EIF4E	2
chr4:99823101	p.T37T,EIF4E	2
chr4:99812406	p.M121I,EIF4E	1
chr4:99802209	p.S102C,EIF4E	1
chr4:99823074	p.T88N,EIF4E	1
chr4:99802262	p.Q46H,EIF4E	1
chr4:99823081	p.S44C,EIF4E	1
chr4:99802265	p.N33K,EIF4E	1
chr4:99806186	p.G228G,EIF4E	1
chr4:99808246	p.T28T,EIF4E	1

Other DBs for Point Mutations

Point Mutation Table of Ensembl: go to Ensembl variation table

Mutation of cBioPortal: go to cBioPortal's Cross-cancer alteration summary

Copy Number for EIF4E in TCGA

* Copy number data were extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered on Jan-05-2015. Function ProcessCNAData in TCGA-Assembler package was used to obtain gene-level copy number value which is calculated as the average copy number of the genomic region of a gene.

cf) Tissue ID[Tissue type]: BLCA[Bladder Urothelial Carcinoma], BRCA[Breast invasive carcinoma], CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], COAD[Colon adenocarcinoma], GBM[Glioblastoma multiforme], Glioma Low Grade, HNSC[Head and Neck squamous cell carcinoma], KICH[Kidney Chromophobe], KIRC[Kidney renal clear cell carcinoma], KIRP[Kidney renal papillary cell carcinoma], LAML[Acute Myeloid Leukemia], LUAD[Lung adenocarcinoma], LUSC[Lung squamous cell carcinoma], OV[Ovarian serous cystadenocarcinoma ], PAAD[Pancreatic adenocarcinoma], PRAD[Prostate adenocarcinoma], SKCM[Skin Cutaneous Melanoma], STAD[Stomach adenocarcinoma], THCA[Thyroid carcinoma], UCEC[Uterine Corpus Endometrial Carcinoma]

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Gene Expression for EIF4E

Gene Expression in Cancer Cell-lines (CCLE)

* CCLE gene expression data were extracted from CCLE_Expression_Entrez_2012-10-18.res: Gene-centric RMA-normalized mRNA expression data.

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Protein Expression Plot (RPPA)

*RPPA protein expression data were extracted from TCPA (The Cancer Proteome Atlas). Normalized data based on replicated based normalization (RBN) was used to draw following figures.

Differential Gene Expression in Primary Tumors (TCGA)

* Normalized gene expression data of RNASeqV2 was extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered at Jan-05-2015. Only eight cancer types have enough normal control samples for differential expression analysis.
(t test, adjusted p<0.05 (using Benjamini-Hochberg FDR))

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CNV vs Gene Expression Plot

* This plots show the correlation between CNV and gene expression.

: Open all plots for all cancer types

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Gene-Gene Network Information

Co-Expressed gene's network Plot

* Co-Expression network figures were drawn using R package igraph. Only the top 20 genes with the highest correlations were shown.
Red circle: input gene, orange circle: cell metabolism gene, sky circle: other gene

: Open all plots for all cancer types


ALG3,ASH2L,BOLA3,BRF2,BUD31,ECE2,EIF4EBP1, LSM1,LSM4,MRPS2,NPM3,POLR2H,PPAPDC1B,PROSC, PSMG3,RPL30,SNHG6,SRM,TCEB1,TIMM44,UBE2S	ACSM2B,ASS1,BSG,IZUMO4,C20orf27,EIF4EBP1,FPGS, GCDH,GLYCTK,MEF2B,MPST,NDRG4,PCBD1,PCYT2, PDZD7,PMM1,PQLC1,PXMP2,RASL10B,RPLP2,TMEM120A

ASH2L,BRF2,CENPM,CYC1,EIF3I,EIF4EBP1,EIF5A, EXOSC4,H2AFZ,KRTCAP3,LSM1,MFSD2B,MRPL12,MRTO4, PROSC,PUSL1,RCC1,RPS6KB2,SRSF9,SRM,ZNF511	AFMID,C19orf48,C9orf142,CCDC34,EIF4EBP1,EXOSC5,FBXW9, GCAT,MPG,MRPS18A,MRPS26,NAT9,NTHL1,PAFAH1B3, PPP5C,PRPS2,SLC35B2,SSBP4,SYNGR2,TMED3,YIPF2

Co-Expressed gene's Protein-protein interaction Network Plot

: Open all plots for all cancer types

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Interacting Genes (from Pathway Commons)

: Open all interacting genes' information including KEGG pathway for all interacting genes from DAVID

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Pharmacological Information for EIF4E

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P06730; -.
Chemistry	ChEMBL	CHEMBL4848; -.
Organism-specific databases	PharmGKB	PA27714; -.
Organism-specific databases	CTD	1977; -.

Drug-Gene Interaction Network

* Gene Centered Interaction Network.

* Drug Centered Interaction Network.

DrugBank ID	Target Name	Drug Groups	Generic Name	Drug Centered Network	Drug Structure
DB01649	eukaryotic translation initiation factor 4E	experimental	7-Methyl-Gpppa
DB01960	eukaryotic translation initiation factor 4E	experimental	7n-Methyl-8-Hydroguanosine-5'-Diphosphate
DB02716	eukaryotic translation initiation factor 4E	experimental	7-Methyl-Guanosine-5'-Triphosphate
DB08217	eukaryotic translation initiation factor 4E	experimental	2,2,5,5-TETRAMETHYL-3-(SULFANYLMETHYL)-2,5-DIHYDRO-1H-PYRROL-1-OL
DB00877	eukaryotic translation initiation factor 4E	approved; investigational	Sirolimus

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Cross referenced IDs for EIF4E

* We obtained these cross-references from Uniprot database. It covers 150 different DBs, 18 categories. http://www.uniprot.org/help/cross_references_section

: Open all cross reference information